Note: Descriptions are shown in the official language in which they were submitted.
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APPAR~T~S P~R R~NOVING OBSTR~CTIONS IN ORGANS
OR BODILY C~VITIES
BACKGROUND OF TEE INVENTION
5For most of the 500,000 plus individuals who suffer
from gallstones, the treatment of choi~e i6 to have a
cholecystectomy, or removal of the gallbladder. Recently,
because of the cost and possible side effects associated
with surgery, methods have been developed for chemically
removing gallstones in situ. Generally, this procedure
requires inserting a catheter into the gallbladder followed
by infusing a chemical solvent capable of dissolving the
gallstone. The procedure thus avoids the need and attendant
risk of surgery.
1~ A variety of chemical solvents have been tried and
found to exhibit varying efficiencies of gallstone
dissolution, depending on the chemical nature of the
gallstone. Gallstones are generally composed of
cholesterol, or calcium salts, particularly calcium
bilirubinate and calcium carbonate. Lipid solvents are
effective at dissolving cholesterol gallstones, whereas
these solvents have little or no solubilizing effect on
gallstones composed of calcium salts. Thus, diethyl ether
readily dis~olves cholesterol gallstones, and other soIvents
such as mono-octanoin and octadiol (glyceryl-l-octyl ether)
have good to outstanding solubilizing properties.
Unfortunately, few if any solvents are satisfactory for
dissolving calcium gallstones.
In addition to the solvents described above suitable
for dissolving cholesterol, recently it has been recognized
tæAKKLpA.Fo6] UC CASE NO. 86-025-1
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that methyl tert butyl ether ~MTBE), a solvent hithertofore
used primarily as a gasoline additive and a chro~atographic
solvent media; was discovered to have outstanding
cholesterol gallstone dissolving properties. Moreover, the
solvent rapidly dissolves the gallstones without damaging
the mucosa of the gallbladder. This finding has led to
considerable activity focused on developing apparatus and
methods for delivering MTBE to patients suffering from
gallstones in ways to most effectively solubilize gal}stones
without the complications arising from introducing a solvent
into the body.
It is obvious that delivering a solvent to a patient
requires the utmost ca~e to avoid releasing the solvent into
the patient's bodily fluids or outside the area of
treatment. Thus a key consideration in developinq devices
used in the chemical therapy of gallstone dissolution i5
ensuring the controlled~delivery and removal of the solvent
used to dissolve the gallstones. Considering that studies
have shown that MTB~E is injurious if it passes into the
intestine where it gets~absorbed which may also be an effect
of other solvents used to solubilize lipids, there is a
critical need for devices that ensure that such chemicals
will not be released during chemical therapy for gallstone
removal.
Also, because of the nPed to ensure containment of the
effective solvent, in addition to the safety features
described above, a suitable device should be ~user
friendly," and not require the presence of highly skilled
technicians to run the device. Further, for the same
reasons, it should be easily maintainable.
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66128-243
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With a little reflection, it becomes apparen~t that there are
considerable hurdles to surmount if one is to develop a device
that has the features described above. For instance, it must be
"intelligent" and capable of sensing instantaneous changes in
gallbladder pressure brought about by infusing the solvent, and
rapidly relay this information to controlling feedback circuits.
This is a crucial feature for such a device. If a gallstone
should in some way prevent the necessary circulation of the
solvent through the gallbladder, a critical pressure will build
up, possibly rupturing the organ, or causing leakage of the
solvent from the gallbladder through the cystic duct into the
common duct and intestine. Thus the device must be "intelligent"
in the sense that it senses gallbladder pressure changes over a
predefined range, and reacts fast enough to~keep the pressure in
that range, shutting down when the pressure is outside the range.
Moreover, ideally, it would be desirable to~have a device that not
only is capable of shutting down, but actually can flush out any
debrls causing the bloclcage, and resume normal operation should
the debris be removed.
SUMMARY OF THE INVENTION
In one aspect, the invention provides apparatus for removal
of a soluble obstruction in a bodily organ or cavity, comprising:
source reservoir means for containing a fluid capable of
dissolving said obstruction; first and second fluid conduits
attached to and forming a fluid circuit with said reservoir means
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66128-243
-3a-
and said organ or cavity and providing fluid communication between
said reservoir means and said organ or cavity; pump means
associated with each of said conduits to move said fluid in said
conduits and around said circuit; means for detecting and
measuring fluid pressure in said organ or cavity, said means
adapted to classify said pressure as high, normal or low according
to predetermined physiological criteria; and means operatively
10 connecting said means for detecting and measuring at each of said
pump means and responsive to said organ or cavity fluid pressure
to cause said pump means to maintain forward fluid flow at low and
normal pressures and to decrease or reverse fluid flow at high
pressure.
A further aspect of the invention provides apparatus for
removal of gallstones from the gallbladder, comprising: a :
reservoir for containing fluid capable of dissolving gallstones;
first and second fluid conduits each having one end communicating
with said reservoir and another end communicating with the
gallbladder; pump means comprising -first and second pumps
operatively associated respectively with said first and second
conduits for moving said fluid in said first conduit in the
infusion direction from said reservoir into the gallbladder, and
for moving said fluid in said second conduit in the aspiration
; direction from the gallbladder to said reservoir; whereby, by
simultaneous infusion and aspiration, continuous withdrawal of
said fluid after exposure to said gallstones can be maintained at
a substantial rate over prolonged periods; said apparatus
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66128-243
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including a control system for selectively inhibiting infusion,
said control system including means for continuously monitoring
pressure within said gal1bladder, means for de-termining the
relationship of said pressure with respect to a desired range
based on predetermined physiological criteria, and means for
selectively inhibiting infusion in response to said pressure being
above said desired range.
The invention also provides, in a gallstone removal apparatus
which includes a liquid transfer system Eor introducing liquid
solvent to and removing said liquid solvent from the gallbladder
of a living patient via a catheter in a manner to cause the
gallstone to disintegrate and be removed with the liquid: the
improvement wherein the liquid transfer system includes a control
system comprising a controller and means for continuously
determining and supplying to the controller the actual liquid
pressure within the gallbladder during the treatment; said
controller having means to receive from the attending operator a
20 pressure setting related to the predetermined pressure at which
flow of the solvent out of the gallbladder into other parts of the
body may occur and said controller being responsive to actual
sensed gallbladder pressure to cause pump means to automatically
reduce the quantity of solvent within said gallbladder upon the
occurrence of actual gallbladder pressure in excess of high
pressure value based upon said setting, thereby preventing release
of said solvent into the body.
The apparatus which is described is effective for therapeutic
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66128~243
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treatment of obstructions in bodily organs by solvent circulation,
particularly gallbladder or common bile duct stones. The
apparatus consists of a forward or reverse acting solvent delivery
means that is linked via pressure transducers to a feedback
controller circuit. Continuous feedback of organ pressure to the
controller circuit by the transducers is determinative of whether
the apparatus acts in the forward or reverse mode.
Another aspect of the invention provides a method for
removing a soluble obstruc~ion in an enclosed space, comprising:
inserting a catheter into said enclosed space, said catheter
having at least two fluid conduits each communicating with source
and receiver reservoir means for containing a fluid suitable for
dissolving said obstruction, said catheter, reservoir means and
conduits forming a fluid circuit; providing a pump in each of said
conduits for moving said fluid through said conduits between said
reservoir and said enclosed space; detecting and measuring fluid
pressure in said enclosed space, said pressure being classified as
high, normal or low according to predetermined criteria; causing
said pumps by means responsive to said high, normal or low
pressure to produce forward fluid flow in said circuit when said
pressure is low or normal and to halt or reverse said fluid flow
when said pressure is h1gh, said fluid thus at normal or low
pressure contacting and dissolving said obstruction.
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The apparatus is preset to perfuse at a set pressure
range. Over this range the solvent is constantly passed from
a reservoir into the gallbladder, and from the gallbladder
it is aspirated to a suitable rece~tacle. Delivery and
removal of the solvent is at a rate sufficient to effect
gallstone dissolution. Shsuld there be an increase in
pressure, a feedback loop activates the device into the
high pressure mode, thereby diverting the solvent away from
the gallbladder. If after a predetermined period of time the
pressure sensing transducer readings from the gallbladder
indicate a return to normal operating pressure range, the
device automatically reinitiates the normal infusion and
aspiration (perfusion) mode. An additionaI feature of the
invention is a self~purging mechanis~ ~After a preset
interval, if the pressure does not decr~ease, the device
enters a reverse mode to purge the aspiration port from the
gallbladder when fluid is aspirated backward through the
infusion port and i~fused through the aspiration port to
purge it ~or discrete short intervals, during which tlme the
pressure in the organ is continuously monitored. Should the
blockage be removable by this ~self-purging~ acSion, the
pressure transducers indicate normal operating pressure, and
the device again resumes action in the normal pressure mode.
However, should the obstruction not be removable, then an
alarm circuit is activated, so notifying the user. A
further feature of the invention is that it is able to
distinguish pressure changes occurring within the
gall~ladder from those arising as a result o~ cou~hing,
laughing or like behavior. This feature prevents needless
changes of operating modes.
12~1~V4~4
BRIEF DESCRIPTION OF ~ ~ DRA~INGS
Figure 1 shows an apparatus suitable for delivering
solvent to a gallbladder and for removing the same
containing dissolved or fragmented gallbladder stones.
Figure 2 shows a controller circuit that regulates the
pump units shown in Figure 1, as well as other features of
the apparatus.
Figures 3, 4 and 5 show features of a 3-lumen
catheter.
DET~ILED DESCRIPTIO~ OF THE INVENTION
The invention described herein is suitably employed for
delivering fluids to organs for removing obstructions
contained therein. It will be appreciated at the outset
that, while the subject invention described below details
the invention regarding the removal of gallstones from the
gallbladder, the invention can be used to remove a variety
of obstructions from organs other than the gallbladder, and
thus should not be construed as being narrowly limited to
the treatment of gallstones. Indeed, it will become readily
apparent that the device is easily adapted to removing
obstructions from organs in general.
The invention deecribed herein is an organ pressure
sensitive apparatus having a solvent delivery means in
constant communication with a controller circuit via
pressure transducers that monitor organ pressura. The
apparatus functions over a preset pressure range delivering
fluid to the gallbladder causing the fluid to contact and
dissolve the gallstones, and withdrawing fluid from the
gallbladder, thereby effecting the removal of dissolved or
fragmented gallstones. The rate of solvent delivery and
[ZAKKLPA.F06] UC CASE NO. 86-025-1
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removal can be adjusted to best effect dissolution of the
obstruction to create the necessary turbulance to dissolve
or fragment gallstones. If the pressure exceeds that of the
normal operating range, the apparatus diverts solvent from
the organ, thereby preventing leakage of the solvent from
the site of treatment. Further, above the normal operating
pressure range, the apparatus can be programmed to be "self-
purging". This may be desirable in the instance when the
obstruction is only partially dissolvable, causing blockage
of the solvent removal, or aspiration means. At lower
pressure, or pressure below the normal operating pressure
range, the rate of aspiration is decreased while infusion
continues, thereby reestablishing normal operating pressure.
Figure 1 shows an exemplary apparatus for removing
gallstones. A reservoir 10 contains a solvent that is a
chemical suitable for dissolving gallstones. Should the
gallstone be composed of cholesterol, a variety of solvents
would be efficacious. Particularly effective is methyl tert
butyl ether (MTBE). The latter, as described su~ra has been
shown to readily dissolve cholesterol stones rapidly both in
vitro and in vivo. At normal operating pressures, the
solvent moves via a con~uit 12 from the reservoir by aid of
a pumping apparatus 14. The fluid then moves through a
valve 16 and from the valve through a catheter into the
gallbladder. During this operation valve 26 is closed to
prevent solvent return to reservoir. The solvent is
delivered at a predetermined effective rate for gallstone
dissolution thereby providing solvent turbulance and contact
with the gallstones for a period of time sufficient to
dissolve and fragment the stones.
[ZAKKLPA.F06] UC CASE N0. 86-025-1
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Simultaneous with the delivery of MTBE to the
gallbladder, a second pump device 18 aspirates the fluid
from the gallbladder now containing dissolved gallstones and
debris. This material passes out of the gallbladder via an
aspiration port in tbe catheter 20. The fluid moves from
the catheter, passing through a valve 23, and from there it
is deposited in a reservoir. Either the reservoir lO used
to deliver the solvent, or a separate reservoir is suitable
for this purpose. Figure l shows the same reservoir lO
being utilized to both deliver fluid to the gallbladder as
well as receive aspirated fluid therefrom. It i~ worth
noting that if the same reservoir is used, gallbladder stone
fragments, mucous and~the like Eemoved from the gallbladder
are heavier than the solvent, MTBE, and therefore settle to
the bottom of the reservoir and do not hinder continued
withdrawal of fluid from the reservoir to effect further
stone dissolution.
The pum~s 14 and 18 are controlled by a controller
circuit 22. `The controller circuit 22 in turn receives
pressure readings from the transducer 24 causing the
controller circuit 22 to open or close flow valves 16, 23
and 26 in a certain fashion to inhi~it infusion or
aspiration as necessary to control organ pressure depending
on whether the transducer 24 indicates that the pressure in
the gallbladder is within, above, or below the normal
operating pressure range. The transducer in turn is
connected to the catheter through port 28 which is in
communication with the ga}lbladder.
At the preset normal operating pressure, the pump 14
delivers fluid from the reservoir lO to the tube 12 through
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the valve 16 and to the gallbladder. Simultaneously, and at
a slightly slower rate, the pump 18 aspirates the fluid from
the gallbladder through the catheter aspira;tion port 20.
Fluid passes through the valve 23 and thence to a reservoir~
The controller is further programmed to respond to
pressures that exceed or are below that of the normal
operating pressure range. Above the normal operating
pressure range (high pres~ure mode), the controller unit 22
shuts down valve 16 and simultaneously opens valve 26~ ~his
provides a path for diverting the incoming fluid away from
the gallbladder. At that time valve 23 is open to effect
continual gallbladder emptyinq to return the pressure to the
normal operating range. If the pressure in the gallbladder
does not return to the normal operating pressure setting
within a preset time, for example, 7 seconds, then the
controller can be ~programmed to instruct the pumps to
reverse the direction of fluid movemen~, and simultaneousl~
valves 23 and 26 are ~losed. Valve 16 is opened to provide
a path for fluid to be reverse aspirated from the
gallbladder in this self-purging~ mode. This mode
essentially causes a small amount of fluid to be pumped in
through the aspiration port of the catheter 20 to clear it
from obstructions while aspiration is effected by pump 14
through valve 16. This mode of operation continues for a
brief period of time, and then the controller unit 22
instructs the machine to resume normal operation should the
obstruction be removed and the pressure transducer 24
indicate reestablishment of normal operating pressure range.
If the transducer continues to indicate pressures present in
the gallbladder, above the normal operating pressure, the
~299V~
controller unit 22 again instructs the pumping apparatus to
purge the system. If, after several "self purging" cycles,
the obstruction is still not removed, the controller unit 22
then shuts down the pumping system and activates an alarm
circuit 34 notifying the user of a potentially dangerous
condition.
Referring now to Figure 1 and Figure 2, a
representative controller unit will be described. The
controller circuit 22 instructs the pumps 14 and 18 to
deliver or aspirate fluid from the gallbladder. Thus, a
circuit will typically have a pressure transducer 30, and an
example of a suitable transducer is a Statham gold pressure
transducer P23ID. The pressure transducer 30 relays
information to an amplication device 32 which amplifies the
signal, and transmits it to a high and low pressure alarm
circuit 34, and either directly or through the averaging
circuit 36, to a pressure-sensing circuit 38 that reads
preset low and high pressure values, and which is connected
to the valves 16, 23, and 26. The latter valves are
typically solenoid flow valves. The averaging circuit 36
can be switched in if desired to discriminate between
pressure changes in the gallbladder arising from fluid
buildup due to obstructions, or from hyperventilating,
laughing or like activities. Thus the averaging circuit
essentially screens out artificially high or low pressure
peaks.
The pressure sensing circuit 38 is connected to a
cascade timer 40, which in turn is connected to a pump
reverse relay circuit 42. Thus, when gallbladder pressure
exceeds that of the normal operating pressure range, and the
~ZAKKLPA.F06] UC CASE NO. 86-025-1
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obstruction is not removed within a few seconds, then the
cascade timer 40 activates the pump reverse relay 42. The
latter circuit is responsible for "self-purging" the system.
Should high pressure persist after several brief "self
purging" cycles, then the alarm circuit 34 is activated,
stopping the pumping system b~v shutting off its power supply
and sounding an alarm notifying the user. Note that at any
time during the pump reverse relay cycle, should the
pressure return to within the normal pressure range, the
apparatus resumes normal operation.
It will be further noted as shown in Figure 2 that a
pump power relay circuit 4~ and a pump speed control circuit
46 are also interactive with the whole system. The pump
speed control circuit 46 derives power through the pump
power relay 44, which in turn is controlled by the alarm
circuit 34. The pump motor 47 derives its power supply
from the pump power relay 44. Any time an alarm condition
exists, this relay shuts off power to the pump, stopping it
from pumping. The pump speed control circuit 46 has a
manual adjustment capability through which the operator can
set the desired perfusion rate for that specific situation.
An analogue pressure readout 48 is provided for the operator
to assess effective operation and to refer to during
calibration.
Several features of an apparatus as described above
that enhance its performance will be described. The pumping
device preferred in the subject invention is a peristaltic
pump. This type of pump offers several advantages such as
replacable wettable surfaces, which are particularly
advantageous in those instances where the solvent being used
[ZAKKLPA.F06] UC CASE NO. 86-025-1
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to dissolve the obstruction is at all corrosive~ ~oreover,
peristaltic pumps are resistant to clogging, in contrast to
standard syringe type pumps. However, it should be noted
that syringe pumps are similarly employable in the subject
invention in those instances where the fluid used to
dissolve and remove the obstruction is a solvent provided
the syringe pumps are constructed of suitable material,
particularly but not exclusively, glass. Syringe pumps made
of plastic are not preferred in instances~where the solvents
used are incompatible with the plastic composition of the
syringe. An additional disadvantage associated with the use
of syringe pumps that is not present in peristaltic pumps is
that in those instance where a solvent is being utilized,
evaporation of the solvent can cause deposits in the body of
the syringe, causing it to ~freeze,~ and thus interrupt
delivery of the fluid to the organ being treated. Lastly,
peristaltic pumps are~ capable of mucb ~reater fluid
circulation rates than a syringe pump. This is advantageous
in certain instances where the obstruction to be removed,
such as a gallstone, re~uires turbulent flow rates across
the surface of the gallstone to accelerate the dissolution
process.
A predetermined normal operating pressu~e range is
programmed into the controller circuit 22. Should the
pressure in the gallbladder exceed normal operating
pressure, the action of the controller circuit 22 prevents
leakage of solvent from the gallbladder through the cystic
duct into the co~mon duct, as well as into the intestine or
around the entry site of the cathetec. Also, because the
controller circuit 'sees" true gallbladder pressure, it
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readily adjusts to decrease as well as increase pressure by
adjusting the net delivery rate of the solvent to the
gallbladder. For example, should the pressure fall below
the normal operating pressure range, the controller circuit
22 ceases or slows down the rate of aspiration of solvent,
and simultaneously continues infusing solvent to reestablish
normal operating pressure.
The pressure sensitive alarm circuit 34 is constantly
monitoring system operation and gallbladder pressure. If
gallbladder pressure cannot be brought to normal operating
pressure range by the action of the controller circuit 22 in
a specified period of time, it will shut down the pumping
system and sound an alarm drawing the attention of the
operator. The operator, after correcting the problem, can
resume normal operation by activating the reset button 49.
The apparatus is completely automatic, and is operable
without any significant operator input. Moreover, it i6
readily converted to a completely closed circuit system in
those instances where the therapeutic fluid is combustible.
Z0 This feature is required for particularly combustible
solvents.
A variety of tubing is suitably used with the pumps o~
the subject apparatus. However, we have found that tubing
composed of TygonTM special formulation F-4040A is
particularly compatible with solvents such as methyl tert
butyl ether. Moreover tubing with a large internal diameter
is favored for use with peristaltic pumps, enabling a high
volume per revolution ratio to be obtained, thereby
permitting a low revolution per minute rate to be utilized,
[ZAKKLPA.F06] UC CASE N0. 86-02S-l
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hence minimizing torque buildup when a switchover to the
high pressure mode leads to pump motor reverse.
As discussed above, the subject apparatus can be
utilized for removing obstructions in a variety of organs.
However, in the instance where it is used to remove
gallstones from gallbladders, perfusion rates of about 50
ml/min - 300 ml/min may be effective. This is readily
accomplished by manually adjusting the pump speed control
circuit 46.
A variety of catheters usable to deliver and aspirate
the fluid can be suitably employed. ~owever, a three lumen
catheter as shown in Figures 3 and 4 is favoced since
pressure measurements, as well as perfusion and aspiration
of the fluid can all be carried out simultaneously. A
lS suitable 3-lumen catheter should have an outside dia~eter
not larger than can be readily employed for the surgical
insertion of the catheter into the gallbladder, and should
have an aspiration port S0, a pressure sensing port 52, and
an infusion port 54. To effectively remove dissolved
gallstQne debris and the like, it is preferred that the
aspiration port be larger in diameter than eitber cf the two
other ports. Figures 4 and 5 further show another feature
of the catheter. It has an elongated tapered tip 56, holes
in the tip 58 and 60 that provide a means for fluid
communication with the pressure sensing port, and the
infusion port, respectively. In addition there are openings
62 in the wall of the catheter that provide a means for
fluid communication of fluid in the gallbladder with the
aspiration port. Note that thè number of openings is not
invariant, and depending on ~he number of gallstones present
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i~99~344
in the gallbladder, as well as the desirable therapeutic
need to effect rapid treatment, that more or fewer holes can
be anticipated.
The system should not be construed as being limited to
a 3-lumen catheter. A variety of catheters of different
lumens will perform satisfactorily provided that the system
is modified to accommodate such catheters, such
modifications being well known to those skilled in the art.
It will be appreciated by those skilled in the art that
there are numerous modifications in both the electrical
circuitry, as well as the overall interconnecting features
of the invention that will achieve the efficacious removal
of obstructions in particular organs. For instance, while
the automatic ~self purging" feature of the apparatus is
desirable, a devioe without this feature will perform
adequa~ely. Moreover, it should be further noted that,
wbile the invention has been described as applicable to the
removal of gallstones from gallbladders, its use should not
be so narrowly construed. Thus, it is the intent herein to
present an invention that is generally applicable for the
removal of obstructions from a variety of organs by
dissolving and dislodging the obstruction using solventsO
We claim:
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